Hitherto, adipose tissue has been considered a mere storage medium for excess energy. However, recent research has elucidated that adipose tissue produces and secretes a variety of physiologically active substances. The physiologically active substances are collectively called adipocytokines, and specific members which have been known to date include leptin, tumor necrosis factor-α (TNF-α), plasminogen-activator inhibitor type 1 (PAI-1), adipsin, and resistin. Some of these adipocytokines, such as leptin, TNF-α, and resistin, have been suggested to be secreted from adipocytes to thereby control sensitivity to insulin.
Adiponectin has recently been identified as an adipocytokine. Adiponectin was originally identified independently by four research groups that used different approaches. Adiponectin cDNA was isolated by large-scale random sequencing of a 3′-directed, human-adipose-tissue cDNA library. Mouse cDNAs for adiponectin termed AcrpSO and AdipoQ were cloned through differential display before and after differentiation of mouse 3T3-L1 and 3T3-F442A cells, respectively. Human adiponectin was also purified from plasma as gelatin-binding protein 28. Obese/diabetic mice and humans exhibit significantly reduced levels of mRNA expression of adiponectin and plasma adiponectin. Lodish et al. have recently reported that a proteolytic cleavage product of Acrp30 increases fatty-acid oxidation in muscle and causes weight loss in mice.
However, whether or not adiponectin is effective in the actual treatment of diabetes remains unknown.
Insulin resistance induced by high-fat diet and accompanied with obesity is a major risk factor for diabetes and cardiovascular diseases, and therefore, capacity to improve insulin resistance is a key factor for determining that a certain drug is effective for the treatment of diabetes.
Accordingly, an object of the present invention is to provide a novel drug which improves insulin resistance and thus is useful in the treatment of diabetes.